DESCRIPTION: (Applicant's Description) The overall objective of this proposal is to evaluate the efficacy of 9-cis retinoic acid (9-cRA) combined with interferon-a (INF-a) as novel treatment for HIV associated Kaposi's sarcoma (KS). We will achieve this objective by conducting two sequential studies. The first study will be a Phase I clinical trial to determine the maximally tolerated dose (MTD) of the combination. The follow up study will be a Phase II clinical trial utilizing the previously determined MTD to measure the antitumor response of combination therapy. Biologic parameters to be measured will include retinoid receptor subtypes on KS tumor tissue, 9-cRA pharmacokinetics, as well as indicators of HIV replication such as p24 antigen and HIV RNA. This proposal is based on preclinical and clinical experience suggesting synergy between INF-a and retinoids as well as preclinical evidence showing that 9-cRA has broader receptor binding and more favorable pharmacokinetics as compared to other retinoids. The investigators collaborating on this proposal have a long and established track record in the conduct of clinical trials in patients with HIV KS. In addition, we have ample patient resources as well as a strong support structure to ensure the successful completion of the proposed research.